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Cytochrome P450 2C19 (CYP2C19)

PG4KDS - Priority Genes

CYP2C19 is an enzyme that is responsible for breaking down (metabolizing) several of the drugs that are commonly used today. Some medications, such as clopidogrel, require activation by CYP2C19 in order for the medication to be effective. Other drugs, such as tricyclic antidepressants (e.g., amitriptyline and imipramine), are metabolized to forms that are not active and are more easily eliminated from the body. There are many other medications that may be affected by CYP2C19 (see this link http://www.pharmgkb.org/gene/PA124).

Over 20 known differences exist in the gene for CYP2C19. These differences in the CYP2C19 gene lead to the production of an enzyme that ranges from completely inactive to overactive. A system designed to classify patients into 4 metabolizer categories based on the ability of their CYP2C19 to break down drugs is used by clinicians to help guide drug therapy decisions.

Priority CYP2C19 genotypes

Poor metabolizers – These patients have little or no working CYP2C19. About 10 percent of people are poor metabolizers.

Drugs we recommend to avoid:

Clopidogrel. Clopidogrel has little to no antiplatelet effect in poor metabolizers of CYP2C19 in these patients in some settings. Other antiplatelet medications (such as prasugrel or ticagrelor) may be alternatives.

Drugs that may need to be avoided:

Amitriptyline. Blood levels of amitriptyline are expected to be high in poor metabolizers of CYP2C19, and side effects are likely. If amitriptyline is used these patients, lower doses may be needed. Amitriptyline dosing is also affected by the CYP2D6 genotype test result.

Other drugs may be affected. The PG4KDS study will evaluate what should be done for the dosing of these other drugs.

Ultra rapid metabolizers – These patients have greater-than-normal CYP2C19 function. About 17 percent of people are ultra rapid metabolizers of CYP2C19.

Drugs that may need to be avoided:

Amitriptyline. Blood levels of amitriptyline are expected to be high in poor metabolizers of CYP2C19, and side effects are likely. If amitriptyline is used these patients, lower doses may be needed. Amitriptyline dosing is also affected by the CYP2D6 genotype test result.

Other drugs may be affected. The PG4KDS study will evaluate what should be done for the dosing of these drugs.

Routine genotypes. Most CYP2C19 medicines don’t need to be adjusted based on the following genotypes:

Intermediate metabolizers – These patients metabolize drugs at a rate somewhere between the poor and extensive metabolizers. About 30 percent of people are intermediate metabolizers.

Extensive metabolizer – These patients have normal CYP2C19 function. About 43 percent of people are extensive metabolizers.